“What do you mean by odd?” asked the Microbiologist vaguely, distracted by all of the requests for coronavirus testing that where sitting in the laboratory.
“Well the patient has bilateral swelling of her face and neck and difficulty swallowing, and it’s a bit odd to be bilateral”.
The Microbiologist perked up and started to pay more attention.
“What does she do? Has she injured herself recently? Does she have pain on opening her mouth? What’s her vaccination history?” he asked.
“Errrr. She’s retired. We haven’t asked about injuries. She can’t open her mouth. She’s 77 years old so we haven’t asked about vaccines” answered the ENT Doctor.
“Okay. Go and ask her the questions. More specifically is she a keen gardener? Has she had any injuries, however minor, which might have been contaminated with soil or manure? When did she last have a tetanus immunisation? I’ll stay on the phone while you ask. This sounds like it might be tetanus”.
There was a pause, then the sound of the phone being put down on the desk, whilst the ENT Doctor went off to get some answers…
The Microbiologist tapped his desk nervously, “see, see not all patients are presenting with Covid-19, and I do wonder how many “ordinary” illnesses are being overlooked amongst the Covid-19 shenanigans…”
The ENT Doctor returned to the phone and asked … “are you still talking to me?”
“Oh umm, no I’m just ranting a little to myself” replied the Microbiologist.
Tetanus (from the Ancient Greek tétanos and teínō meaning “I stretch”) is a toxin mediated disease caused by the bacterium Clostridium tetani. This means it is actually the toxin that causes the symptoms rather than the bacterium itself. If the bacterium does not have the genes to produce toxin it does not have the ability to produce toxin and therefore cannot cause tetanus. C. tetani is a spore producing, anaerobic, Gram-positive bacterium which survives for months and years in the environment, especially in soil. Disease occurs when bacterial spores are inoculated into a wound which then germinate producing a neurotoxin that spreads around the patient’s body.
Tetanus is uncommon in countries with established immunisation campaigns; the tetanus vaccine was introduced in the UK in 1961. Unlike a lot of vaccines (e.g. MMR, pertussis, Hib) that protect by inducing “herd immunity” so that the infection cannot circulate in the community, tetanus vaccine only protects the person vaccinated. As tetanus is acquired from the environment, there is no person-to-person spread; herd immunity makes no difference to the incidence of tetanus.
In England and Wales there are about 10 cases of tetanus a year, mainly in the over 65 year olds who are no longer sufficiently vaccinated… and have plenty of time to garden!
The tetanus neurotoxin essentially blocks certain nerve cells that would stop muscles firing all the time; the result is unrestricted positive stimulation of the muscles which ultimately go into spasm. It sounds complicated but I found a simple (and short) video that helps to explain it further. It also contains what opisthotonus is, I’m sure this is a yoga pose the Editor-Chief-in-Charge (aka Wife) does…she also loves gardening!? But I digress…
How does tetanus present?
Tetanus occurs 3-21 days after a tetanus prone injury (see below under prevention). Sometimes there is no obvious history of an injury as there doesn’t need to be many bacteria to produce a lot of toxin.
There are 4 main types of presentation with tetanus:
- Generalised – this is the most common form characterised by muscle spasms, especially of the face and neck (known as trismus) which can cause facial grimacing (known as risus sardonicus or the sardonic grin) progressing to affect the muscles of the chest and abdomen. Spams are made worse by sensory stimulation such as bright lights and noise. Spasms can cause painful arching of the back such that the patient’s body lifts off the bed with only the feet and back of the head touching the surface (called opisthotonus). Autonomic dysfunction occurs with changes the heart rate and blood pressure as well as causing breathing difficulties.
- Localised – muscle spasm and rigidity only occur at the site of bacterial inoculation
- Cephalic – cranial nerve abnormalities due to wound contamination specifically on the head
- Neonatal – trismus, spasms, difficulty feeding and convulsions in babies shortly after birth
Tetanus is a severe infection with a high mortality and long-term neurological sequelae. The mortality in adults is highest in the frail and elderly and in those in whom there has been a short incubation period (as this represents severe contamination and a high bacterial burden), or a delay in diagnosis and treatment. The current mortality in the UK in adults is 11%. The most severe form of tetanus is neonatal which has an 80% mortality with brain damage in 20% of the survivors; fortunately this is a rare condition.
One of the scariest parts to tetanus is that consciousness is not affected which as you can imagine is both painful and terrifying for these patients!
How do you diagnose tetanus?
The key to diagnosing tetanus is to think about it. Anyone who presents with a clinical condition consistent with tetanus should be investigated in order to confirm or exclude the diagnosis.
However detecting the bacterium C. tetani is not that simple. Detection can be done directly using molecular tests such as PCR on wound tissue however there can be a lot of toxin production from very few bacteria; the amount of actual bacteria in the sample may be too little for the PCR to detect. It’s not a great test.
“So just grow the bacterium in culture, that’s what you lab guys do, isn’t it?”… Actually, it can be very difficult to grow C. tetani in the microbiology laboratory! It’s not always easy to find lesions on the patient to sample (tissue or swab) plus C. tetani dies very quickly when exposed to air. C. tetani is a strict anaerobe; usually an hour in air is enough to kill the bacterium. This means that the bacterium is often dead long before it reaches the laboratory and even if it reaches the laboratory alive it is very hard to keep it alive! If by some chance the laboratory does manage to grow the bacterium that is not diagnostic in itself, the culture needs to be tested using PCR to see if bacterium has the genes to produce the toxin. If the PCR is positive for toxin genes then the diagnosis of tetanus is confirmed.
Another way to diagnose tetanus is to look for the neurotoxin in the patient’s blood. This isn’t that easy either! A bio-assay is done at the Reference Laboratory in which serum from the patient is inoculated into mice, some are then given antitoxin (protects against tetanus) while the rest are not. If the mice given antitoxin are protected from tetanus, whilst those not given antitoxin develop tetanus, then the diagnosis of tetanus is confirmed.
There are ethical issues with these types of tests as it results in the death of all the mice, however at present there is no other test for detecting the toxin directly. If this test is going to be done then it is imperative that the patient’s blood samples are taken before they are given intravenous immunoglobulin; immunoglobulin messes with the test, making the test negative despite them actually having tetanus!
How do you treat tetanus?
Tetanus is a medical emergency which requires urgent treatment before the diagnosis is confirmed; if you suspect it clinically, treat it!
There are 5 main aspects to the management of tetanus:
- Wound debridement – if possible remove as much bacterial burden as you can; less bacteria means less toxin
- Antibiotics – to kill off any bacteria; usually either IV Benzylpenicillin or IV Metronidazole or even both.
- Intravenous immunoglobulin – this is the mainstay of treatment; the immunoglobulin binds toxin in the patient’s blood stream preventing it from affecting the nerves. Immunoglobulin doesn’t reverse the neurological symptoms that have already occurred but it stops the infection progressing. In the past there was a specific anti-tetanus immunoglobulin for this purpose but this is no longer available in the UK and instead we now use normal IV immunoglobulin at the doses shown in the table below. Remember: don’t give immunoglobulin before taking blood to test for tetanus, it neutralises the toxin in the sample and makes the bio-assay negative… and the mice are killed for no reason… and the Reference Laboratory quite rightly get very upset!
- Supportive care – to control spasms and keep the patient calm. It is a good idea to nurse these patients in quiet, dimly lit rooms. In severe cases it is necessary to paralyse and ventilate these patients on ITU for their comfort!
- Post-infection vaccination – whilst this may sound odd as surely the infection is its own immune booster it is still necessary to artificially boost the patient’s immune system after tetanus. The vaccine is actually more immunogenic than the disease and will help prevent any future infection.
IVIg Products tested for anti-tetanus antibodies in adults (Volume required in ml)
NB product selection depends on availability
For individuals < 50kg
For individuals > 50kg
Intratect 5%, OR
Flebogamma 5%, OR
Octagam 5%, OR
Gammaplex 5%, OR
Intratect 10%, OR
Flebogamma 10%, OR
Octagam 10%, OR
Privigen 10%, OR
Panzyga 10%, OR
Tetanus is preventable. The mainstay of prevention is vaccination as part of the childhood vaccination program. In the UK children receive tetanus vaccine at 2, 3, and 4 months, and then pre-school (3-5 years) and as a teenager (13-18 years). These 5 doses of vaccine should give long-term protection.
If someone then sustains a potentially contaminated wound (known as tetanus prone wounds) then they require further preventative treatment including:
- Thorough cleaning and delayed closure (24-48 hours) if possible to allow air into the wound
- Intramuscular Tetanus Immunoglobulin (IM-TIG) to give passive antibody to neutralise any toxin (the infamous jab in your bum!)
- Tetanus booster vaccine if not received full 5 doses of childhood vaccines OR received 5 doses but the last dose >10 years previously
- Puncture wounds contaminated with soil or manure e.g. whilst gardening
- Wounds containing foreign bodies e.g. wood splinters, rose thorns
- Compound fractures
- Wounds or burns with extensive devitalised tissue (the blood and hence oxygen supply has been compromised)
- Animal bites or scratches where the animals mouth or claws might be contaminated with soil
- Intravenous drug abusers who have contaminated the drugs with soil
So the ENT Doctor, ignored the Microbiologist’s ranting about Covid-19 and continued the story...
“She is a keen gardener. She has recently been putting manure onto her roses and managed to cut her foot with her garden fork a week or so ago. She can’t remember when she last had a tetanus immunisation but definitely not for many years… do you think I could write this up?”
“Well before you do that, as this is a medical emergency, let’s get on and treat your patient shall we…?” said the Microbiologist patiently… being thankful he was dealing with something other than Covid-19!
There are 2 great guidelines in the UK for managing tetanus; the first is from Public Health England and the second is from the “Green Book” the UK National guideline for vaccinations.